SLC12A6 encodes a potassium-chloride cotransporter (KCC3) that mediates electroneutral K+-Cl- symport activated by cell swelling, contributing to cell volume homeostasis 1. The transporter functions across plasma membranes and is involved in ion homeostasis in multiple tissues including red blood cells and nervous system cells 2. Biallelic SLC12A6 mutations cause autosomal-recessive hereditary motor and sensory neuropathy with corpus callosum agenesis (Andermann syndrome), characterized by infantile-onset peripheral neuropathy and central nervous system involvement 3. Heterozygous variants produce dominant Charcot-Marie-Tooth (CMT) disease with remarkable phenotypic heterogeneity depending on specific mutations 4. The Gly552Asp variant causes late-onset, sensory-predominant axonal neuropathy 5, while Arg207His causes severe childhood-onset demyelinating neuropathy 64. Functional studies in Xenopus oocytes demonstrate these mutations significantly reduce potassium influx capacity 56. Clinically, SLC12A6-related CMT presents with variable onset (ages 1-45 years) and severity, with some patients developing intellectual disability or epilepsy alongside neuropathy 7. This phenotypic diversity across different mutations is unprecedented among CMT genes. Genetic screening for SLC12A6 is recommended in CMT patients, particularly those with concurrent central nervous system manifestations 7.